Compositions and methods for treating wrinkles and/or fine lines of the skin

ABSTRACT

Compositions which contain an agonist substance of one or a number of receptors associated with a chlorine channel are useful for slackening and/or relaxing cutaneous tissue, and in particular for the purpose of treating wrinkles and fine lines of the skin. Such compositions can be administered topically or by injection. Preferred agonists include glycine, serine, taurine, β-alanine, N-(benzyloxycarbonyl)glycine (Z-glycine), gamma-aminobutyric acid (GABA), isoguvacine, isonipecotic acid, 4,5,6,7-tetrahydroisoxazolo 5,4-c!pyrid-3(2H)-one, benzodiazepines, steroids, and barbiturates. The composition can additionally contain a retinoid and/or a hydroxy acid.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to the use of substances which areagonists of a receptor associated with a chlorine channel in a cosmeticand/or dermatological composition, in particular for the purpose oftreating wrinkles and fine lines of the skin, and to cosmetic and/ordermatological compositions which contain such a substance.

Discussion of the Background

Women, and indeed even men, are currently inclined to wish to appearyoung for as long as possible and consequently are looking to soften thesigns of ageing of the skin, which are reflected in particular bywrinkles and fine lines. In this respect, advertising and fashionpresent products intended to retain a radiant and wrinkle-free skin,these being the signs of young skin, for as long as possible, all themore so since physical appearance has an effect on mental attitudeand/or on morale. It is consequently important to feel physically andspiritually young.

Until now, wrinkles and fine lines have been treated using cosmeticproducts containing active agents which act on the skin, for example bymoisturizing it or by improving its cell renewal or alternatively bypromoting the synthesis of collagen of which the cutaneous tissue iscomposed. However, to date, it is not known to act on wrinkles byinvolving the muscle components present in the skin.

It is known that the platysma muscles of the face are under the controlof the motor nerve afferent activity of the facial nerve and that,moreover, the interlobular septa of the hypoderm contain within themfibers which constitute a striated muscle tissue (panniculus carnosus).Moreover, it is also known that a subpopulation of fibroblasts of thedermis, known as myofibroblasts, has characteristics in common with themuscle tissue.

The Applicants have observed, in certain pathological and therapeuticsituations, the role played, as regards the wrinkles of the face, by thenerves controlling all this muscle tissue. Thus, in attacks on thefacial nerve, in which transmission of the nerve impulse is interruptedand/or weakened, a paralysis of the muscles of the face is witnessed inthe area of innervation. This facial paralysis is reflected, among otherclinical indications, by an alleviation in, indeed disappearance of, thewrinkles.

On the other hand, in muscle hypercontraction conditions of the face,the Applicants have observed an accentuation in the wrinkles of theface. Moreover, an accentuation in the wrinkles of the face has alsobeen observed in muscle hypertonia conditions of Parkinson's disease andside-effects induced by neuroleptics.

Moreover, it has been shown that botulinus toxin, originally used fortreating spasms, could have an effect on muscle spasticity conditions(see A. Blitzer et al., Arch. Otolaryngol. Head Neck Surg., vol 119,pages 1018 to 1022 (1993)) and on the wrinkles of the glabella, whichare intersuperciliary wrinkles (see J. D. Carruters et al., J. Dermatol.Sura. Oncol., vol. 18, pages 17 to 21 (1992)). It is consequentlypossible, by pharmacological action, to have an effect on the nervecomponent of wrinkles. Botulinus toxin acts directly at the level of theneuro-muscular junction by blocking the action of acetylcholine onmuscular tenseness.

The junction between a nerve and a muscle constitutes the myoneuralendplate, before which is found the afferent nerve route known as themotor neuron. Moreover, the cell membranes of each nerve fiber containmany ionic channels, and in particular chlorine channels, capable ofallowing the corresponding element to pass through in the ionic form,and, in the case of chlorine channels, in the chloride form. Neuronalreceptors are associated with these channels. The neuronal receptorsassociated with the chlorine channels are in particular receptors forglycine (glycine-strychnine sensitive receptors) and receptors for GABA(GABA_(A) receptors).

Moreover, it is known that, in the central nervous system, it ispossible to decrease the excitability of the neuron by variouspharmacological agents which have an effect on the glycine-strychninesensitive receptors or on the GABA_(A) receptors of the central nervoussystem (see W. Sieghart, Trends in Pharmacological Science, vol. 131,pages 446 to 450 (December 1992)). Activation of these receptors opensthe chlorine channels and leads to the entry of chloride ions, whichresults in an increase in the chloride ions in the cells of the nervefiber and thus to hyperpolarization of the neurons, which consequentlybecome less excitable.

On the other hand, in the neuromuscular junction, a decrease inexcitability of the motor neuron leads to a lessened stimulation of themuscle fiber, thus causing it to slacken.

However, to date no completely suitable compositions or methods areavailable for treating wrinkles and/or fine lines of the skin. Thus,there remains a need for methods and compositions effective for treatingwrinkles and/or fine lines of the skin.

SUMMARY OF THE INVENTION

Accordingly, it is one object of the present invention to provide novelcompositions for treating wrinkles and/or fine lines of the skin.

It is another object of the present invention to provide novel methodsfor treating wrinkles and/or fine lines of the skin.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat contractile muscle fibers, which are under the direct control ofthe neuromotor impulse, play an essential role in the pathogenesis ofwrinkles and that suppression of the neuromotor impulse alleviates notonly wrinkles but also fine lines and also has a "smoothing" effect onthe cutaneous microrelief. It has also been found that cutaneous tissuescontain receptors associated with chlorine channels, something which,until now, had not been envisaged. It has thus been found that it ispossible to act on these channels in order to slacken or relax thesetissues and thus to lessen wrinkles and fine lines.

Until now, a connection between the chlorine channels of nerve fibers ofthe peripheral cutaneous nervous system and wrinkles had never beenestablished, nor had it been found that it was possible to treatwrinkles by acting on chlorine channels by activation of the receptorswhich are found in or in the neighborhood of these channels. Substanceswhich can activate the receptors of chlorine channels and thus lead tothe entry of chloride into cells are known as agonist substances.

Consequently, the present invention provides topical cosmetic ordermatological compositions, which contain at least one agonistsubstance of at least one receptor associated with at least one chlorinechannel present in cutaneous tissue except glycine andgamma-aminobutyric acid for relaxing and/or slackening cutaneous tissue.

In another aspect, the present invention provides injectable cosmetic ordermatological compositions, for the purpose of lessening wrinklesand/or fine lines, which contain at least one agonist substance of atleast one receptor associated with at least one chlorine channel presentin cutaneous tissue for relaxing and/or slackening cutaneous tissue. Inthis context, the term "injectable" means suitable for injection intotissue, and in particular in wrinkles.

The present invention further provides injectable or topical cosmetic ordermatological compositions, which contain at least one agonistsubstance of at least one receptor associated with at least one chlorinechannel of at least one cutaneous afferent nerve pathway for relaxingand/or slackening cutaneous tissue.

The present invention additionally provides topical cosmetic ordermatological compositions for the purpose of lessening wrinkles and/orfine lines which contain at least one agonist substance of at least onereceptor associated with at least one chlorine channel of at least onecutaneous afferent nerve pathway, except glycine and gamma-butyric acid,for relaxing and/or slackening cutaneous tissue.

The compositions containing the agonist according to the presentinvention can be applied topically or by subcutaneous and/or intradermaland/or "intrawrinkle" injection.

Another aspect of the present invention is a method for the cosmetictreatment of wrinkles and/or fine lines in humans by injecting acomposition containing at least one agonist substance of at least onereceptor associated with at least one chlorine channel present incutaneous tissue.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A number of receptors associated with the chlorine channel exist. Theyconcern in particular glycine strychnine sensitive receptors andGABA_(A) receptors, the latter themselves containing a number ofsubunits comprising the GABA site, the benzodiazepine site, a type ofsteroid site and the barbiturates site. All the substances which act asagonists of these receptors or sites can be used for slackening orrelaxing cutaneous tissues in accordance with the present invention.

For a substance to be recognized as an agonist of a receptor of thechlorine channel, it must exhibit the following two characteristics:

(i) to be able to be bound selectively to at least one of the variousreceptors associated with the chlorine channel; and

(ii) to show a relaxation effect on a contracted muscle tissue.

The first characteristic, which consists of the possibility of beingbound to a receptor associated with a chlorine channel, does not make itpossible to distinguish an agonist activity from an antagonist activitybut it does make it possible to define a potential affinity for thereceptor.

The second characteristic makes it possible to select the agonists. Theagonist activity of the substance under study can be demonstrated by therelaxation effect which it produces on a muscle tissue which has beencontracted beforehand by a chlorine channel antagonist substance.Substances known as chlorine channel antagonists can be chosen as suchand in particular include the following substances: bicuculline,strychnine, tert-butylbicyclophosphorothionate and picrotoxin.

Mention may be made, as agonist substances, which can be used in thepresent invention for activating glycine-strychnine sensitive receptors,of glycine, serine, taurine, β-alanine, and N-(benzyloxycarbonyl)glycineor (Z-glycine).

Mention may be made, as agonist substances, which can be used in theinvention for activating GABA_(A) receptors, of gamma-aminobutyric acid(GABA), isoguvacine, isonipecotic acid, 4,5,6,7-tetrahydroisoxazolo5,4-c!pyrid-3(2H)-one (THIP), benzodiazepines such as nitrazepam(1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one), diazepam(7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one),flunitrazepam(5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one)or oxazepam(7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one),certain steroids such as alfaxalone (3-hydroxypregnane-11,20-dione) orbarbiturates such as barbital (5,5-diethylbarbituric acid),pentobarbital (5-ethyl-5-(1-methylbutyl)barbituric acid) orphenobarbital (5-ethyl-5-phenylbarbituric acid), and their salts.

It is certainly known to use GABA and glycine in combination with otheractive agents for combating ageing of the skin but, until now, theiraction in relaxing and slackening cutaneous tissues for the purpose oftreating wrinkles was not known. The generally known actions areinhibition of elastase, the effect on collagen, and cell renewal.

Indeed, it is known in the state of the art to use amino acids asmoisturizing agents for the purpose of improving the condition of theskin. In particular, combinations of amino acids such as glycine,taurine or β-alanine in the form of peptide mixtures have been used incosmetic compositions intended for treating the ageing of the skin.Thus, FR-A-2,546,164 discloses the elastase-inhibiting properties oflipopeptides which prevent deterioration of elastin fibers in the skin,which makes them antiwrinkle active agents. Moreover, U.S. Pat. No.5,198,465 discloses that amino acids prevent deficiencies in thesynthesis of collagen, which consequently makes it possible to preventageing of the skin.

In addition, JP-A-05043448 discloses that the combination of GABA and ofdiisopropylamine facilitates renewal of the skin and thus preventscutaneous ageing.

In the compositions according to the present invention, the agonist of areceptor associated with the chlorine channel is preferably used in anamount ranging from 0.00001 to 20% by weight, based on the total weightof the composition, and in particular in an amount ranging from 0.01 to10% by weight, based on the total weight of the composition.

The compositions according to the present invention can be provided inall the pharmaceutical dosage forms normally used for a topical orinjectable application.

The amounts of the various constituents of the compositions according tothe present invention are those conventionally used in the fields underconsideration and are appropriate to their pharmaceutical dosage form.

For topical application, the compositions of the present inventioncomprise a medium compatible with skin. These compositions can beprovided in particular in the form of aqueous, alcoholic oraqueous/alcoholic solutions, of gels, of water-in-oil or oil-in-wateremulsions having the appearance of a cream or of a gel, ofmicroemulsions or of aerosols or alternatively in the form of vesiculardispersions containing ionic and/or nonionic lipids. Thesepharmaceutical dosage forms are prepared according to the conventionalmethods in the fields under consideration.

The present compositions for topical application can constitute inparticular a cosmetic or dermatological protection, treatment or carecomposition for the face, for the neck, for the hands or for the body(for example day creams, night creams, sun creams or oils or bodymilks), a make-up composition (for example foundation cream), or anartificial tanning composition.

When the composition of the present invention is an emulsion, theproportion of fatty substance which it contains can range from 5% to 80%by weight, and preferably from 5% to 50% by weight, based on the totalweight of the composition. The fatty substances and the emulsifiers usedin the composition in the emulsion form are chosen from thoseconventionally used in the cosmetic or dermatological field.

Mention may be made, as fatty substances which can be used in thepresent invention, of mineral oils (paraffin), vegetable oils (karitebutter liquid fraction) and their hydrogenated derivatives, animal oils,synthetic oils (perhydrosqualene), silicone oils (dimethylpolysiloxane),and fluorinated oils. Mention may also be made, as other fattysubstances, of fatty alcohols (cetyl alcohol or stearyl alcohol), fattyacids (stearic acid), and waxes.

The emulsifiers can be present in the present compositions in aproportion ranging from 0.3% to 30% by weight, and preferably from 0.5to 30% by weight, based on the total weight of the composition.

In a conventional way, the cosmetic or dermatological compositions ofthe present invention can also contain adjuvants which are typical inthe corresponding fields, such as hydrophilic or lipophilic gellingagents, preservatives, antioxidants, solvents, fragrances, fillers,screening agents, and colorants. Moreover, these compositions cancontain hydrophilic or lipophilic active agents. The amounts of thesevarious adjuvants or active agents are those conventionally used in thecosmetics or dermatological field and, for example, from 0.01% to 20% ofthe total weight of the composition. These adjuvants or these activeagents, depending on their nature, can be introduced into the fattyphase, into the aqueous phase and/or into lipid vesicles.

Mention may especially be made, among the active agents which thecompositions of the invention can contain, of active agents having aneffect on the treatment of wrinkles or of fine lines and in particularof keratolytic active agents. The term "keratolytic active agent" isunderstood to mean an active agent having desquamative, exfoliative orscrubbing properties or an active agent capable of softening the corneallayer.

Mention may in particular be made, among these active agents having aneffect on the treatment of wrinkles or fine lines which the compositionsof the invention can contain, of hydroxy acids and retinoids.

The hydroxy acids can be, for example, α-hydroxy acids or β-hydroxyacids, which can be linear, branched or cyclic and saturated orunsaturated. The hydrogen atoms of the carbon chain can, in addition, besubstituted by halogens or halogenated, alkyl, acyl, acyloxy,alkoxycarbonyl or alkoxy radicals having from 2 to 18 carbon atoms.

The hydroxy acids which can be used are in particular glycolic, lactic,malic, tartaric, citric, 2-hydroxyalkanoic, mandelic, and salicylicacids, and their acyl derivatives, such as 5-n-octanoylsalicylic acid,5-n-dodecanoylsalicylic acid, 5-n-decanoylsalicylic acid,5-n-octylsalicylic acid, 5-or 4-n-heptyloxysalicylic acid or2-hydroxy-3-methylbenzoic acid, or alternatively their alkoxyderivatives such as 2-hydroxy-3-methoxybenzoic acid.

The retinoids can be in particular retinoic acid (all trans or 13-cis)and its derivatives, retinol (vitamin A) and its esters such as retinolpalmitate, retinol acetate, and retinol propionate, and their salts.

These active agents can be used in particular at concentrations rangingfrom 0.0001% to 5% by weight based on the total weight of thecomposition.

When the compositions of the present invention are intended to beinjected, they can be provided in the form of solutions containing theexcipients commonly used for injections and for example in the form ofan isotonic sodium chloride solution.

Other features of the invention will become apparent in the course ofthe following descriptions of exemplary embodiments which are given forillustration of the invention and are not intended to be limitingthereof.

EXAMPLES

The amounts indicated in the following Examples are percentages byweight. The term "qsp for 100%" means that that ingredient is present inan amount sufficient to make the total amount of all ingredients equal100% by weight.

Example 1

Care lotion for the face.

    ______________________________________    Z-Glycine                8%    Antioxidant            0.05%    Preservative            0.3%    Ethanol (solvent)        8%    Water              qsp for  100%    ______________________________________

The lotion obtained has an effect on wrinkles during repeated use (twicedaily applications for one month).

Example 2

Gel for caring for the face.

    ______________________________________    Z-Glycine                   5%    Hydroxypropylcellulose (Klucel H sold by                                1%    the company Hercules) (gelling agent)    Preservative               0.3%    Ethanol (solvent)           15%    Antioxidant               0.05%    Water                 qsp for  100%    ______________________________________

The gel obtained has an effect on wrinkles. It can be applied daily,morning and evening, for one month.

Example 3

Care cream for the face (oil-in-water emulsion).

    ______________________________________    Flunitrazepam               0.1%    Glyceryl stearate (emulsifier)                                 2%    Polysorbate 60 (Tween 60 sold by                                 1%    the company ICI) (emulsifier)    Stearic acid                1.4%    Triethanolamine (neutralizing agent)                                0.7%    Carbomer (Carbopol 940 sold by the company                                0.4%    Goodrich)    Karite butter liquid fraction                                 12%    Perhydrosqualene             12%    Preservative                0.3%    Fragrance                   0.5%    Antioxidant                0.05%    Water                  qsp for  100%    ______________________________________

A white oily cream is obtained which has an effect on wrinkles and finelines and which can be applied daily.

Example 4

Care cream for the face (oil-in-water emulsion).

    ______________________________________    Flunitrazepam              0.2%    Glycercyl mono- and distearate                                2%    Cetyl alcohol              1.5%    Cetylstearyl alcohol/cetylstearyl alcohol                                7%    oxyethylenated 33 EO    Dimethylpolysiloxane       1.5%    Liquid paraffin           17.5%    Preservative               0.3%    Fragrance                  0.5%    Glycerol                  12.5%    Water                 qsp for  100%    ______________________________________

This application is based on French Patent Application 94-11742 filed onSep. 30, 1994, which is incorporated herein by reference in itsentirety.

Obviously, numerous modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that, within the scope of the appended claims, theinvention may be practiced otherwise than as specifically describedherein.

What is claimed as new and desired to be secured by Letters Patent ofthe United States is:
 1. A method for relaxing or slackening cutaneoustissue, comprising topically applying a cutaneous tissue relaxing orslackening effective amount of at least one agonist substance of atleast one receptor associated with at least one chlorine channel presentin cutaneous tissue, wherein the agonist substance is selected from thegroup consisting of serine, taurine, β-alanine,N-(benzyloxycarbonyl)glycine, isoguvacine, isonipecotic acid,4,5,6,7-tetrahydroisoxazolopyrid-3 (2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 2. The method of claim 1, wherein said agonistsubstance activates a glycine-strychnine sensitive receptor and isselected from the group consisting of serine, taurine, β-alanine, andN-(benzyloxycarbonyl)glycine.
 3. The method of claim 1, wherein saidagonist substance is applied in a composition in an amount ranging from0.00001 to 20% by weight, based on the total weight of said composition.4. The method of claim 3, wherein said agonist substance is present insaid composition in an amount ranging from 0.01 to 10% by weight, basedon the total weight of said composition.
 5. The method of claim 3,wherein said composition further comprises at least one of a hydroxyacid and a retinoid.
 6. The method of claim 5, wherein said hydroxy acidis selected from the group consisting of α-hydroxy acids and β-hydroxyacids, which can be linear, branched or cyclic and saturated orunsaturated.
 7. The method of claim 5, wherein said retinoid is selectedfrom the group consisting of retinoic acid, retinol and retinol esters.8. A method for lessening wrinkles or fine lines, by relaxing orslackening cutaneous tissue comprising topically applying a wrinkle orfine line lessening effective amount of at least one agonist substanceof at least one receptor associated with at least one chlorine channelof at least one cutaneous afferent nerve pathway, wherein the agonistsubstance is selected from the group consisting of serine, taurine,β-alanine, N-(benzyloxycarbonyl)glycine, isoguvacine, isonipecotic acid,4,5,6,7-tetrahydroisoxazolo- 5,4-c!pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 9. The method of claim 8, wherein said agonistsubstance activates a glycine-strychnine sensitive receptor and isselected from the group consisting of serine, taurine, β-alanine, andN-(benzyloxycarbonyl)glycine.
 10. The method of claim 8, wherein saidagonist substance is applied in a composition in an amount ranging from0.00001 to 20% by weight, based on the total weight of said composition.11. The method of claim 10, wherein said agonist substance is present insaid composition in an amount ranging from 0.01 to 10% by weight, basedon the total weight of said composition.
 12. The method of claim 10,wherein said composition further comprises at least one of a hydroxyacid or a retinoid.
 13. The method of claim 12, wherein said hydroxyacid is selected from the group consisting of α-hydroxy acids andβ-hydroxy acids, which can be linear, branched or cyclic and saturatedor unsaturated.
 14. The method of claim 12, wherein said retinoid isselected from the group consisting of retinoic acid, retinol and retinolesters.
 15. A method for lessening wrinkles or fine lines, comprisingadministering by injection a cosmetic or dermatological composition,said composition comprising at least one agonist substance of at leastone receptor associated with at least one chlorine channel present incutaneous tissue, wherein the agonist substance is selected from thegroup consisting of serine, taurine, β-alanine,N-(benzyloxycarbonyl)glycine, isoguvacine,isonipecotic acid,4,5,6,7-tetrahydroisoxazolopyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 16. The method of claim 15, wherein said agonistsubstance activates a glycine-strychnine sensitive receptor and isselected from the group consisting of serine, taurine, β-alanine, andN-(benzyloxycarbonyl)glycine.
 17. The method of claim 15, wherein saidagonist substance is present in said composition in an amount rangingfrom 0.00001 to 20% by weight, based on the total weight of saidcomposition.
 18. The method of claim 15, wherein said agonist substanceis present in said composition in an amount ranging from 0.01 to 10% byweight, based on the total weight of said composition.
 19. The method ofclaim 15, wherein said composition further comprises at least one of ahydroxy acid or a retinoid.
 20. The method of claim 19, wherein saidhydroxy acid is selected from the group consisting of α-hydroxy acidsand β-hydroxy acids, which can be linear, branched or cyclic andsaturated or unsaturated.
 21. The method of claim 19, wherein saidretinoid is selected from the group consisting of retinoic acid, retinoland retinol esters.
 22. A method for relaxing or slackening cutaneoustissue, comprising administering by injection a cosmetic ordermatological composition, said composition comprising at least oneagonist substance of at least one receptor associated with at least onechlorine channel of at least one cutaneous afferent nerve pathway,wherein the agonist substance is selected from the group consisting ofserine, taurine, β-alanine, N-(benzyloxycarbonyl)glycine, isoguvacine,isonipecotic acid, 4,5,6,7-tetrahydroisoxazolo 5,4-c!pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 23. The method of claim 22, wherein said agonistsubstance activates a glycine-strychnine sensitive receptor and isselected from the group consisting of serine, taurine, β-alanine, andN-(benzyloxycarbonyl)glycine.
 24. The method of claim 22, wherein saidagonist substance is present in said composition in an amount rangingfrom 0.00001 to 20% by weight, based on the total weight of saidcomposition.
 25. The method of claim 22, wherein said agonist substanceis present in said composition in an amount ranging from 0.01 to 10% byweight, based on the total weight of said composition.
 26. The method ofclaim 22, wherein said composition further comprises at least one of ahydroxy acid and a retinoid.
 27. The method of claim 26, wherein saidhydroxy acid is selected from the group consisting of α-hydroxy acidsand β-hydroxy acids, which can be linear, branched or cyclic andsaturated or unsaturated.
 28. The method of claim 26, wherein saidretinoid is selected from the group consisting of retinoic acid, retinoland retinol esters.
 29. A method for the cosmetic treatment of wrinklesor fine lines in humans, comprising injecting a composition comprisingat least one agonist substance of at least one receptor associated withat least one chlorine channel present in cutaneous tissue, wherein theagonist substance is selected from the group consisting of serine,taurine, β-alanine, N-(benzyloxycarbonyl)glycine, isoguvacine,isonipecotic acid, 4,5,6,7-tetrahydroisoxazolo 5,4-c!pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 30. The method of claim 1, wherein said agonistsubstance activates a GABA_(A) receptor and is selected from the groupconsisting of isoguvacine, isonipecotic acid,4,5,6,7-tetrahydroisoxazolo 5,4-c!pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 31. The method of claim 8, wherein said agonistsubstance activates a GABA_(A) receptor and is selected from the groupconsisting of isoguvacine, isonipecotic acid,4,5,6,7-tetrahydroisoxazolo 5,4-c!pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 32. The method of claim 15, wherein said agonistsubstance activates a GABA_(A) receptor and is selected from the groupconsisting of gamma-aminobutyric acid, isoguvacine, isonipecotic acid,4,5,6,7-tetrahydroisoxazolo 5,4-c!pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxypregnane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 33. The method of claim 22, wherein said agonistsubstance activates a GABA_(A) receptor and is selected from the groupconsisting of gamma-aminobutyric acid, isoguvacine, isonipecotic acid4,5,6,7- tetrahydroisoxazolo pyrid-3(2H)-one,1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,5-(2-flurophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one,7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one,3-hydroxopregane-11,20-dione, 5,5-diethylbarbituric acid,5-ethyl-5-(1-methylbutyl)barbituric acid, 5-ethyl-5-phenylbarbituricacid, and their salts.
 34. The method of claim 1, wherein said receptoris at least one selected from the group consisting of GABA_(A) receptorsand glycine-strychnine sensitive receptors.